Tag Archives: Gang Zheng

Shape-shifting nanoparticles for better chemotherapy from the University of Toronto (Canada)

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A research team from the University of Toronto and its shape-shifting nanoparticles are being touted in a Feb. 19, 2016 news item on Nanowerk,

Chemotherapy isn’t supposed to make your hair fall out — it’s supposed to kill cancer cells. A new molecular delivery system created at U of T [University of Toronto] Engineering could help ensure that chemotherapy drugs get to their target while minimizing collateral damage.

Many cancer drugs target fast-growing cells. Injected into a patient, they swirl around in the bloodstream acting on fast-growing cells wherever they find them. That includes tumours, but unfortunately also hair follicles, the lining of your digestive system, and your skin.

U of T Engineering Professor Warren Chan has spent the last decade figuring out how to deliver chemotherapy drugs into tumours — and nowhere else. Now his lab has designed a set of nanoparticles attached to strands of DNA that can change shape to gain access to diseased tissue.

A Feb. 18, 2016 University of Toronto news release (also on EurekAlert), which originated the news item, expands on the theme,

“Your body is basically a series of compartments,” says Chan. “Think of it as a giant house with rooms inside. We’re trying to figure out how to get something that’s outside, into one specific room. One has to develop a map and a system that can move through the house where each path to the final room may have different restrictions such as height and width.”

One thing we know about cancer: no two tumours are identical. Early-stage breast cancer, for example, may react differently to a given treatment than pancreatic cancer, or even breast cancer at a more advanced stage. Which particles can get inside which tumours depends on multiple factors such as the particle’s size, shape and surface chemistry.

Chan and his research group have studied how these factors dictate the delivery of small molecules and nanotechnologies to tumours, and have now designed a targeted molecular delivery system that uses modular nanoparticles whose shape, size and chemistry can be altered by the presence of specific DNA sequences.

“We’re making shape-changing nanoparticles,” says Chan. “They’re a series of building blocks, kind of like a LEGO set.” The component pieces can be built into many shapes, with binding sites exposed or hidden. They are designed to respond to biological molecules by changing shape, like a key fitting into a lock.

These shape-shifters are made of minuscule chunks of metal with strands of DNA attached to them. Chan envisions that the nanoparticles will float around harmlessly in the blood stream, until a DNA strand binds to a sequence of DNA known to be a marker for cancer. When this happens, the particle changes shape, then carries out its function: it can target the cancer cells, expose a drug molecule to the cancerous cell, tag the cancerous cells with a signal molecule, or whatever task Chan’s team has designed the nanoparticle to carry out.

…

“We were inspired by the ability of proteins to alter their conformation — they somehow figure out how to alleviate all these delivery issues inside the body,” says Chan. “Using this idea, we thought, ‘Can we engineer a nanoparticle to function like a protein, but one that can be programmed outside the body with medical capabilities?’”

Applying nanotechnology and materials science to medicine, and particularly to targeted drug delivery, is still a relatively new concept, but one Chan sees as full of promise. The real problem is how to deliver enough of the nanoparticles directly to the cancer to produce an effective treatment.

“Here’s how we look at these problems: it’s like you’re going to Vancouver from Toronto, but no one tells you how to get there, no one gives you a map, or a plane ticket, or a car — that’s where we are in this field,” he says. “The idea of targeting drugs to tumours is like figuring out how to go to Vancouver. It’s a simple concept, but to get there isn’t simple if not enough information is provided.”

“We’ve only scratched the surface of how nanotechnology ‘delivery’ works in the body, so now we’re continuing to explore different details of why and how tumours and other organs allow or block certain things from getting in,” adds Chan.

He and his group plan to apply the delivery system they’ve designed toward personalized nanomedicine — further tailoring their particles to deliver drugs to your precise type of tumour, and nowhere else.

Here are links to and citations for the team’s two published papers,

DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction by Seiichi Ohta, Dylan Glancy, Warren C. W. Chan. Science  19 Feb 2016: Vol. 351, Issue 6275, pp. 841-845 DOI: 10.1126/science.aad4925

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology by Edward A. Sykes, Qin Dai, Christopher D. Sarsons, Juan Chen, Jonathan V. Rocheleau, David M. Hwang, Gang Zheng, David T. Cramb, Kristina D. Rinker, and Warren C. W. Chan. PNAS     doi: 10.1073/pnas.1521265113 published online Feb. 16, 2016.

Both papers are behind paywalls.

Microbubbles reform into nanoparticles after bursting

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It seems researchers at the Toronto-based (Canada), Princess Margaret Cancer Centre, have developed a new theranostic tool made of microbubbles used for imaging that are then burst into nanoparticles delivering therapeutics. From a March 30, 2015 news item on phys.org,

Biomedical researchers led by Dr. Gang Zheng at Princess Margaret Cancer Centre have successfully converted microbubble technology already used in diagnostic imaging into nanoparticles that stay trapped in tumours to potentially deliver targeted, therapeutic payloads.

The discovery, published online today [March 30, 2015] in Nature Nanotechnology, details how Dr. Zheng and his research team created a new type of microbubble using a compound called porphyrin – a naturally occurring pigment in nature that harvests light.

A March 30, 2015 University Health Network news release on EurekAlert, which originated the news item, describes the laboratory research on mice,

In the lab in pre-clinical experiments, the team used low-frequency ultrasound to burst the porphyrin containing bubbles and observed that they fragmented into nanoparticles. Most importantly, the nanoparticles stayed within the tumour and could be tracked using imaging.

“Our work provides the first evidence that the microbubble reforms into nanoparticles after bursting and that it also retains its intrinsic imaging properties. We have identified a new mechanism for the delivery of nanoparticles to tumours, potentially overcoming one of the biggest translational challenges of cancer nanotechnology. In addition, we have demonstrated that imaging can be used to validate and track the delivery mechanism,” says Dr. Zheng, Senior Scientist at the Princess Margaret and also Professor of Medical Biophysics at the University of Toronto.

Conventional microbubbles, on the other hand, lose all intrinsic imaging and therapeutic properties once they burst, he says, in a blink-of-an-eye process that takes only a minute or so after bubbles are infused into the bloodstream.

“So for clinicians, harnessing microbubble to nanoparticle conversion may be a powerful new tool that enhances drug delivery to tumours, prolongs tumour visualization and enables them to treat cancerous tumours with greater precision.”

For the past decade, Dr. Zheng’s research focus has been on finding novel ways to use heat, light and sound to advance multi-modality imaging and create unique, organic nanoparticle delivery platforms capable of transporting cancer therapeutics directly to tumours.

Interesting development, although I suspect there are many challenges yet to be met such as ensuring the microbubbles consistently arrive at their intended destination in sufficient mass to be effective both for imaging purposes and, later, as nanoparticles for drug delivery purposes.

Here’s a link to and citation for the paper,

In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging by Elizabeth Huynh, Ben Y. C. Leung, Brandon L. Helfield, Mojdeh Shakiba, Julie-Anne Gandier, Cheng S. Jin, Emma R. Master, Brian C. Wilson, David E. Goertz, & Gang Zheng. Nature Nanotechnology (2015) doi:10.1038/nnano.2015.25 Published online 30 March 2015

This paper is behind a paywall but a free preview is available via ReadCube Access.

This is one of those times where I’m including the funding agencies and the ‘About’ portions of the news release,

The research published today was funded by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship, the Emerging Team Grant on Regenerative Medicine and Nanomedicine co-funded by the CIHR and the Canadian Space Agency, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research, the International Collaborative R&D Project of the Ministry of Knowledge Economy, South Korea, the Joey and Toby Tanenbaum/Brazilian Ball Chair in Prostate Cancer Research, the Canada Foundation for Innovation and The Princess Margaret Cancer Foundation.

About Princess Margaret Cancer Centre, University Health Network

The Princess Margaret Cancer Centre has achieved an international reputation as a global leader in the fight against cancer and delivering personalized cancer medicine. The Princess Margaret, one of the top five international cancer research centres, is a member of the University Health Network, which also includes Toronto General Hospital, Toronto Western Hospital and Toronto Rehabilitation Institute. All are research hospitals affiliated with the University of Toronto. For more information, go to http://www.theprincessmargaret.ca or http://www.uhn.ca .

I was not expecting to see South Korea or Brazil mentioned in the funding. Generally, when multiple countries are funding research, their own research institutions are also involved. As for the Princess Margaret Cancer Centre being one of the top five such centres internationally, I wonder how these rankings are determined.

Heat and light signifying much from a new nanoparticle at the University of Toronto

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Paraphrasing from Shakespeare’s play MacBeth for this piece is a stretch but I can’t resist. The title comes from the speech MacBeth gives on hearing of his wife’s death (from The Tragedy of MacBeth webpage on the MIT website),

… Out, out, brief candle!
Life’s but a walking shadow, a poor player
That struts and frets his hour upon the stage
And then is heard no more: it is a tale
Told by an idiot, full of sound and fury,
Signifying nothing. [emphasis mine]

Enough of the digression. Scientists at the Princess Margaret Hospital and the University of Toronto, have engineered a nanoparticle that uses light and heat to destroy tumours and light and sound to find and image tumours. From the March 20, 2011 news release on the University of Toronto website,

“In the lab, we combined two naturally occurring molecules (chlorophyll and lipid) to create a unique nanoparticle that shows promise for numerous diverse light-based (biophotonic) applications,” Professor [Gang] Zheng said. “The structure of the nanoparticle, which is like a miniature and colourful water balloon, means it can also be filled with drugs to treat the tumor it is targeting.”

It works this way, explains first author Jonathan Lovell, a doctoral student at IBBME [Institute of Biomaterials & Biomedical Engineering] and OCI [Ontario Cancer Institute]: “Photothermal therapy uses light and heat to destroy tumors. With the nanoparticle’s ability to absorb so much light and accumulate in tumors, a laser can rapidly heat the tumor to a temperature of 60 degrees and destroy it. The nanoparticle can also be used for photoacoustic imaging, which combines light and sound to produce a very high-resolution image that can be used to find and target tumors.”

Here’s what makes this such a breakthrough,

This nanomaterial is also non-toxic, explained Professor Warren Chan of IBBME, another author of the paper. “Jon Lovell and Gang Zheng created a material that doesn’t have metals, [which] means no toxins, but with similar tunable properties to its metal nanostructure brother,” he said. This is the first reported organic nanostructure with such a unique feature, he noted, and so provides a significant opportunity to explore unique designs of organic nanostructures for biomedical applications without concerns regarding toxicity.

I recently mentioned Professor Zheng’s work in the context of a recent funding announcement from the Canadian Space Agency and the Canadian Institutes of Health Research in my March 17, 2011 posting.

If I recall rightly and this is a pretty simple explanation, organic chemistry includes the element of carbon while inorganic excludes it.

Canadian Space Agency funds nanomedicine?

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I suppose it’s ignorance but I can’t quite fathom why the Canadian Space Agency (CSA) [ETA March 17, 2011: Corrected the mane of the Agency from Canada Space Agency to Canadian Space Agency] is partnering with the Canadian Institutes of Health Research (CIHR) to fund nanomedicine. I don’t understand how that fits into the CSA’s mandate. The March 16, 2011 news item on Nanowerk doesn’t answer my questions,

Research on nanomedicine and regenerative medicine is designed to prevent disease and improve human health. Nanomedicine delivers medical technologies that detect or function at the molecular level to diagnose and treat disease, while regenerative medicine stimulates the renewal of bodily tissues and organs or restores function through natural and bioengineered means. Various innovations in these areas have helped combat vascular diseases, cancer, diabetes, multiple sclerosis and other chronic diseases. By promoting research in these areas, CIHR and CSA will be moving Canada to the forefront of modern medical research. [emphasis mine]

When was the Space Agency mandated to bring Canada to the “forefront of modern medical research?” I did look at the projects to see if any of them might have a ‘space travel’ component,

This funding will enable researchers to potentially:

# Identify microlesions in multiple sclerosis, using a new tool for quantifying the cause of the disease and how well a treatment is working, Dr. Daniel Côté, Université Laval;

# Create personalized nanomedicines that silence cancer-causing genes, Dr. P[ieter] Cullis, University of British Columbia;

# Develop microchip-based devices to analyze prostate cancer markers in blood, Dr. Shana Kelley, University of Toronto;

# Generate transplantable, insulin-producing cells from stem cells for diabetes, Dr. Timothy Kieffer, University of British Columbia;

# Develop innovative sensorimotor rehabilitation approaches for patients with spinal cord injuries or stroke, Dr. Serge Rossignol, Université de Montréal;

# Study how novel therapeutic interventions can regenerate blood vessels, Dr. Michael Sefton, University of Toronto; and,

# Develop nanotechnology-enabled image-guided methods of diagnosing and treating lung cancer and vascular diseases, Dr. Gang Zheng, University Health Network.

I suppose the project to regenerate blood vessels might have some applications appropriate for space travel/exploration but the rest leave me puzzled. If anyone has an answer or even a guess, please do leave a comment.

ETA March 17, 2011: I found the CSA’s mandate here,

The mandate of the Canadian Space Agency is:

To promote the peaceful use and development of space, to advance the knowledge of space through science and to ensure that space science and technology provide social and economic benefits for Canadians.